The Critical Role of Solubility in Saving Time and Cost in the Development of Antibody-Drug Conjugates (ADCs)

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Antibody-Drug Conjugates (ADCs) combine the specificity of monoclonal antibodies with the potent cytotoxic effects of small molecule drugs. Due to the sophisticated nature of these new modalities, both the challenges and the costs of development are higher compared to more traditional therapeutics. Optimizing solubility early can positively impact development by improving ADC stability, pharmacokinetics, manufacturability, and therapeutic performance.

Insoluble ADCs cause:

  • aggregation, leading to reduced stability and increased immunogenicity
  • inefficient drug loading and release, resulting in suboptimal therapeutic effects
  • poor pharmacokinetics, including reduced circulation time and increased off-target toxicity
  • complications in manufacturing, leading to higher production costs and inconsistency in product quality.

Soluble ADCs enable:

  • enhanced stability, reducing the risk of immunogenic responses
  • optimal drug loading and controlled release, maximizing treatment effectiveness
  • efficient circulation in the bloodstream, enhancing target specificity and therapeutic efficacy
  • optimized manufacturability, leading to consistent synthesis, purification and formulation with reduced production costs and accelerated time-to-market.

Allocating enough resources to thoroughly investigate the solubility profiles of ADC components during the early stages of development optimizes downstream processes and prevents attrition. By modifying the payload and choosing a linker to increase the solubility of an ADC without compromising potency – stability, pharmacokinetics, manufacturability, and therapeutic performance can all be enhanced from the onset – talk to our experts.

 

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